ID NRAM_IADGE STANDARD; PRT; 96 AA. AC P03480; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 16-MAY-2006, entry version 46. DE Neuraminidase (EC 3.2.1.18) (Fragment). GN Name=NA; OS Influenza A virus (strain A/Duck/Germany/49 H10N7). OC Viruses; ssRNA negative-strand viruses; Orthomyxoviridae; OC Influenzavirus A. OX NCBI_TaxID=11356; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX MEDLINE=83023028; PubMed=6896994; RA Blok J., Air G.M.; RT "Variation in the membrane-insertion and 'stalk' sequences in eight RT subtypes of influenza type A virus neuraminidase."; RL Biochemistry 21:4001-4007(1982). RN [2] RP REVIEW. RX PubMed=15567494; DOI=10.1016/j.virusres.2004.08.012; RA Nayak D.P., Hui E.K., Barman S.; RT "Assembly and budding of influenza virus."; RL Virus Res. 106:147-165(2004). RN [3] RP REVIEW. RX PubMed=16192481; DOI=10.1056/NEJMra050740; RA Moscona A.; RT "Neuraminidase inhibitors for influenza."; RL N. Engl. J. Med. 353:1363-1373(2005). RN [4] RP REVIEW. RX PubMed=15744059; DOI=10.1248/bpb.28.399; RA Suzuki Y.; RT "Sialobiology of influenza: molecular mechanism of host range RT variation of influenza viruses."; RL Biol. Pharm. Bull. 28:399-408(2005). CC -!- FUNCTION: Catalyzes the removal of terminal sialic acid residues CC from viral and cellular glycoconjugates. Cleaves off the terminal CC sialic acids on the glycosylated HA during virus budding to CC facilitate virus release. Additionally helps virus spread through CC the circulation by further removing sialic acids from the cell CC surface. These cleavages prevent self-aggregation and ensure the CC efficient spread of the progeny virus from cell to cell. CC Otherwise, infection would be limited to one round of replication. CC Described as a receptor-destroying enzyme because it cleaves a CC terminal sialic acid from the cellular receptors. May facilitate CC viral invasion of the upper airways by cleaving the sialic acid CC moities on the mucin of the airway epithelial cells. Likely to CC plays a role in the budding process through its association with CC lipid rafts during intracellular transport. May additionally CC display a raft-association independent effect on budding. Plays a CC role in the determination of host range restriction on replication CC and virulence. Sialidase activity in late endosome/lysosome CC traffic seems to enhance virus replication. CC -!- CATALYTIC ACTIVITY: Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, CC alpha-(2->8)- glycosidic linkages of terminal sialic residues in CC oligosaccharides, glycoproteins, glycolipids, colominic acid and CC synthetic substrates. CC -!- COFACTOR: Binds 1 calcium ion (By similarity). CC -!- ENZYME REGULATION: Inhibited by the neuraminidase inhibitors CC zanamivir (Relenza) and oseltamivir (Tamiflu). These drugs CC interfere with the release of progeny virus from infected cells CC and are effective against all influenza strains. Resistance to CC neuraminidase inhibitors is quite rare. CC -!- SUBUNIT: Homotetramer (By similarity). CC -!- SUBCELLULAR LOCATION: Type II membrane protein. Preferentially CC accumulates at the apical plasma membrane in infected polarized CC epithelial cells, which is the virus assembly site. Uses lipid CC rafts for cell surface transport and apical sorting. In the CC virion, forms a mushroom-shaped spike on the surface of the CC membrane (By similarity). CC -!- DOMAIN: Intact N-terminus is essential for virion morphogenesis. CC Possess two apical sorting signals, one in the ectodomain, which CC is likely to be a glycan, and the other in the transmembrane CC domain. The transmembrane domain also plays a role in lipid raft CC association (By similarity). CC -!- PTM: N-glycosylated (By similarity). CC -!- MISCELLANEOUS: The influenza A genome consist of 8 RNA segments. CC Genetic variation of hemagglutinin and/or neuraminidase genes CC results in the emergence of new influenza strains. The mechanism CC of variation can be the result of point mutations or the result of CC genetic reassortment between segments of two different strains. CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 34 family. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J02099; AAA43391.1; -; Genomic_RNA. DR InterPro; IPR001860; Glyco_hydro_34. DR Pfam; PF00064; Neur; 1. DR ProDom; PD000431; Glyco_hydro_34; 1. KW Calcium; Glycoprotein; Glycosidase; Hydrolase; Membrane; KW Metal-binding; Signal-anchor; Transmembrane; Virion protein. FT CHAIN 1 >96 Neuraminidase. FT /FTId=PRO_0000078685. FT TOPO_DOM 1 6 Cytoplasmic (Potential). FT TRANSMEM 7 35 Signal-anchor for type II membrane FT protein (Potential). FT TOPO_DOM 36 >96 Extracellular (Potential). FT REGION 11 33 Involved in apical transport and lipid FT raft association (By similarity). FT REGION 36 89 Hypervariable stalk region. FT REGION 90 >96 Head of neuraminidase. FT CARBOHYD 47 47 N-linked (GlcNAc...) (Potential). FT CARBOHYD 56 56 N-linked (GlcNAc...) (Potential). FT CARBOHYD 57 57 N-linked (GlcNAc...) (Potential). FT CARBOHYD 67 67 N-linked (GlcNAc...) (Potential). FT CARBOHYD 68 68 N-linked (GlcNAc...) (Potential). FT CARBOHYD 87 87 N-linked (GlcNAc...) (Potential). FT NON_TER 96 96 SQ SEQUENCE 96 AA; 10472 MW; F6382279F093C552 CRC64; MNPNQKLFAL SGVAIALSVM NLLIGISNVG LNVSLHLKEK GTKQEENLTC TTITQNNTTV VENTYVNNTT IITKEPDLKA PSYLLLNHSL CSVEGW //